Integrated genetic profiling of archival pediatric high-grade glial tumors and reassessment with 2021 WHO classification of paediatric CNS tumours.

Though rare, pediatric high-grade gliomas (pHGG) are a leading cause of cancer-related mortality in children. We wanted to determine whether our currently available clinical laboratory methods could better define diagnosis for pHGG that had been archived at our institution for the past 20 years (1998 to 2017). We investigated 33 formalin-fixed paraffin-embedded pHGG using ThermoFisher Oncoscan SNP microarray with somatic mutation analysis, Sanger sequencing, and whole genome sequencing. These data were correlated with historical histopathological, chromosomal, clinical, and radiological data. Tumors were subsequently classified according to the 2021 WHO Classification of Paediatric CNS Tumours. All 33 tumors were found to have genetic aberrations that placed them within a 2021 WHO subtype and/or provided prognostic information; 6 tumors were upgraded from WHO CNS grade 3 to grade 4. New pHGG genetic features were found including two small cell glioblastomas with H3 G34 mutations not previously described; one tumor with STRN-NTRK2 fusion; and a congenital diffuse leptomeningeal glioneuronal tumor without a chromosomal 1p deletion but with KIAA1549-BRAF fusion. Overall, the combination of laboratory methods yielded key information for tumor classification. Thus, even small studies of these uncommon tumor types may yield new genetic features and possible new subtypes that warrant future investigations.

Maintaining a methods database to optimize solid tumor tissue culture: Review of a 15-year database from a single institution.

Chromosome analysis of solid tumors provides valuable information for diagnosis and patient management, yet successfully culturing solid tumors can be challenging. The Children's Mercy (CM) Cytogenetics laboratory has compiled a database of 1371 non-lymphoma solid tumors cultured since 2002. Analysis of the tumor culture data found a culture success rate of 91.6%. Abnormal karyotypes were identified in 47.0% of these tumors. A quality improvement project reviewed the database for methods, cell culture success, yield of clonally abnormal karyotypes, culture failure, tumor diagnostic category, and other. This review revealed processes that could be optimized with minor changes to methods in a subset of tumors. Three tumor/method pair examples are provided including adrenal cortical carcinomas (ACCs), choroid plexus tumors (CPTs), and neuroblastoma. The successful culture of tumors as defined by capture of clonally abnormal cells is dependent upon several factors including culture medium, monolayer versus suspension culture, length of time in culture, method of disaggregation and other. The database serves as a quality assurance tool that enables continuous improvement in culture success rate and abnormal yield. It is also an educational resource for laboratory technologists, residents and fellows. Using the database to track methods and results ensures consistency in routine tumor processing, facilitates oversight to optimize methods for quality, and improves results for patient care.

Interdisciplinary Parkinson's Disease Deep Brain Stimulation Screening and the Relationship to Unintended Hospitalizations and Quality of Life.

OBJECTIVE: To investigate the impact of pre-operative deep brain stimulation (DBS) interdisciplinary assessments on post-operative hospitalizations and quality of life (QoL). BACKGROUND: DBS has been utilized successfully in Parkinson's disease (PD) for the treatment of tremor, rigidity, bradykinesia, off time, and motor fluctuations. Although DBS is becoming a more common management approach there are no standardized criteria for selection of DBS candidates, and sparse data exist to guide the use of interdisciplinary evaluations for DBS screening. We reviewed the outcomes of the use of an interdisciplinary model which utilized seven specialties to pre-operatively evaluate potential DBS candidates. METHODS: The University of Florida (UF) INFORM database was queried for PD patients who had DBS implantations performed at UF between January 2011 and February 2013. Records were reviewed to identify unintended hospitalizations, falls, and infections. Minor and major concerns or reservations from each specialty were previously documented and quantified. Clinical outcomes were assessed through the use of the Parkinson disease quality of life questionnaire (PDQ-39), and the Unified Parkinson's Disease Rating Score (UPDRS) Part III. RESULTS: A total of 164 cases were evaluated for possible DBS candidacy. There were 133 subjects who were approved for DBS surgery (81%) following interdisciplinary screening. There were 28 cases (21%) who experienced an unintended hospitalization within the first 12 months following the DBS operation. The patients identified during interdisciplinary evaluation with major or minor concerns from any specialty service had more unintended hospitalizations (93%) when compared to those without concerns (7%). When the preoperative "concern" shifted from "major" to "minor" to "no concerns," the rate of hospitalization decreased from 89% to 33% to 3%. A strong relationship was uncovered between worsened PDQ-39 at 12 months and increased hospitalization. CONCLUSIONS: Unintended hospitalizations and worsened QOL scores correlated with the number and severity of concerns raised by interdisciplinary DBS evaluations. The data suggest that detailed screenings by interdisciplinary teams may be useful for more than just patient selection. These evaluations may help to stratify risk for post-operative hospitalization and QoL outcomes.

Relationship of Body Mass Index to Clinical Outcomes after Infliximab Therapy in Patients with Crohn's Disease.

BACKGROUND & AIMS: There are conflicting data for the role of obesity in Crohn's disease (CD) and the effect on long-term clinical outcomes is poorly studied. Some evidence suggests obesity is associated with diminished responsiveness to biological agents, especially anti-tumour necrosis factor antibodies. METHODS: We aimed to examine the influence of body mass index (BMI) on the response to infliximab in CD in a retrospective analysis. The outcomes of interest within 12 months were: (1) Composite loss of response (CD-related flare or surgery; LOR); (2) any CD-related surgery (CDRS); and (3) CD-related intestinal resectional surgery (CDRIS). RESULTS: A total of 388 patients were included. The mean BMI was 24.2kg/m(2) [± standard deviation (SD) 5.1]. Of the 388 patients, 137 (35.4%) were overweight (BMI: 25-29.9kg/m(2)) or obese (BMI: ≥30kg/m(2))-160 (41.6%) patients had LOR during the 12 months follow-up; 121 (31.4%) required CDRS, and 109 (28.2%) required CDRIS. Multivariate analysis showed that increasing BMI (per unit, kg/m(2) increase) reduced the risk of LOR [odds ratio (OR): 0.98], CDRS (OR: 0.95), and CDRIS (OR: 0.95). Rates for all outcomes were higher, but not significantly so, in the extreme categories (underweight and obese) and lower in the underweight categories compared with normal BMI. Exclusion of the obese category of patients strengthened this relationship. CONCLUSIONS: Body mass index at first infusion of infliximab has a non-linear relationship with outcomes at 12 months. The worst outcomes are at the extremes of weight (underweight and obese categories). Increasing BMI is associated with a modest reduction in risk of LOR, CDRS, and CDRIS within 12 months, increasing with the exclusion of the obese category.

Ultrasound-Guided Thoracic Paravertebral Blockade: A Retrospective Study of the Incidence of Complications.

BACKGROUND: The benefits of thoracic paravertebral block (TPVB) have been demonstrated for patients undergoing surgery for breast cancer. However, pleural puncture resulting in pneumothorax is a serious complication associated with traditional approaches using guidance from anatomic landmarks and nerve stimulation and may contribute to the low utilization of this block. An ultrasound-guided technique has the potential to reduce complications by providing direct visualization of the paravertebral space during needle manipulation. We evaluated the complications using a single-injection, transverse, in-plane ultrasound-guided technique for paravertebral blockade in patients undergoing mastectomy with immediate reconstruction for breast cancer treatment or prophylaxis. METHODS: Data from all patients who underwent TPVB between January 1, 2010, and December 3, 2013, at Massachusetts General Hospital was prospectively recorded in a computerized database. All blocks were placed for postoperative analgesia after unilateral or bilateral mastectomy with immediate breast reconstruction. Medical records were retrospectively reviewed for any patient who developed complications including accidental pleural puncture, symptomatic pneumothorax, hypotension, or bradycardia, as well as signs and symptoms of toxicity or effects of local anesthetic outside of the paravertebral space. RESULTS: Eight hundred fifty-six patients underwent a total of 1427 thoracic paravertebral injections (285 unilateral and 571 bilateral TPVB). There were 6 complications (0.70%; 99.2% confidence interval, 0.17%-1.86%) including symptomatic bradycardia and hypotension (n = 3), vasovagal episode (n = 1), and evidence of possible local anesthetic toxicity (n = 2). There was no incidence of suspected accidental pleural puncture or symptomatic pneumothorax identified in our study population. CONCLUSIONS: The routine use of a single-injection, transverse, in-plane ultrasound-guided technique for TPVB in patients undergoing mastectomy with immediate breast reconstruction is associated with very few complications.

Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients.

OBJECTIVE: To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life. BACKGROUND: There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method. METHODS: An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery. RESULTS: Eighty-six percent (44/51) of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18%) patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005). The rate of hospitalization revealed a direct relationship to the "level of concern"; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046) and 12 months (p = 0.027) when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed. CONCLUSIONS: The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further prospective comparative and larger studies are required to confirm our results.

Costs of adalimumab versus infliximab as first-line biological therapy for luminal Crohn's disease.

BACKGROUND AND AIMS: Randomised controlled trials demonstrate that the anti-tumour necrosis factor-α (anti-TNFα) therapies infliximab and adalimumab are effective in inducing remission and preventing relapse of Crohn's disease (CD). As few studies have compared costs and efficacy of these two drugs directly, we examined this issue. METHODS: Data were collected for patients receiving either drug as first-line anti-TNFα for CD. Patients were matched as closely as possible on age, gender, weight, height, and date of commencement of therapy. Response to induction therapy was assessed at 12weeks, and sustained clinical benefit at last point of follow-up. Resource data were collected for all patients until study end, with National Health Services reference costs applied to calculate the total cost per patient with adalimumab compared with infliximab. RESULTS: Thirty-six patients had been treated with adalimumab as first-line anti-TNFα since 2010. We matched an identical number of infliximab patients. Demographic data were similar between the two groups. Costs were significantly lower with adalimumab (£6692.95 less per patient (95% confidence interval £1816.61-£11569.29)), which was largely driven by the drug costs and drug administration costs associated with infliximab. Twenty-nine (80.6%) patients responded to induction therapy with both drugs, and 22 (61.1%) achieved glucocorticosteroid-free sustained clinical benefit with either drug at last point of follow-up. CONCLUSIONS: Costs of infliximab used as first-line anti-TNFα therapy are greater, which may have implications for selection. Clinical outcomes appeared comparable, although power to detect a statistically significant difference would be limited.

Use of preoperative paravertebral block decreases length of stay in patients undergoing mastectomy plus immediate reconstruction.

BACKGROUND: A prior study in patients undergoing breast surgery with and without the use of paravertebral blocks (PVB) found no significant difference in patient length of stay (LOS). However, patients undergoing bilateral procedures and those undergoing immediate reconstructions were excluded. We sought to determine if the use of PVB in patients undergoing unilateral or bilateral mastectomy plus immediate reconstruction decreases patient LOS. METHODS: We undertook a retrospective review of patients who had mastectomies with immediate reconstructions with and without the use of preoperative PVB. Outcomes including LOS, postoperative nausea and vomiting, and time to oral narcotics were compared between groups. RESULTS: Mean LOS for the PVB group was 42 h. This was significantly less than the mean LOS of 47 h for the nonblock group (p = .0015). The significantly lower LOS for the PVB group was true for patients undergoing bilateral procedures (p = .045), unilateral procedures (p = .0031), tissue expander placement (p = .0114), and immediate implant placement (p = .037). Mean time to conversion to oral narcotics was significantly shorter in the PVB group (15 h) compared with the nonblock group (20 h) (p < .001). The incidence of postoperative nausea in the PVB group (42.8 %) was also significantly less than in the nonblock group (54.7 %) (p = .031). CONCLUSIONS: The routine use of preoperative PVB in patients undergoing mastectomy plus immediate reconstruction significantly decreased patient LOS. In addition to improved pain control from the block itself, quicker conversion to oral narcotics because of less postoperative nausea likely contributed to a decreased LOS.

Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn's disease: a large single centre experience.

BACKGROUND: Infliximab is licenced for use in Crohn's disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging. AIM: To examine these issues in a large cohort of patients who received infliximab for CD. METHODS: A retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey-Bradshaw Index (HBI) of ≥ 2 points. Remission was defined as an HBI ≤ 4. Physician's global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan-Meier plots and univariate and multivariate analyses. RESULTS: Overall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI ≤ 4, indicating remission, at last point of follow-up (median 24 months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6 months of therapy (P=0.03). An inflammatory disease phenotype (P=0.04 univariate analysis, P=0.03 Kaplan Meier analysis) and male gender (P=0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few. CONCLUSION: In this single centre study, infliximab was efficacious and well-tolerated in CD.

Adalimumab as second line anti-tumour necrosis factor alpha therapy for Crohn's disease: A single centre experience.

BACKGROUND AND AIMS: Non-response, loss of response, or intolerance to anti-tumour necrosis factor alpha (anti-TNFα) therapy is well recognised in Crohn's disease (CD) patients. Data concerning outcomes following the use of a second anti-TNFα therapy, particularly in patients who do not respond to a first anti-TNFα agent, are still emerging. The aim of this study was to assess response and tolerability to adalimumab following infliximab failure in a single centre cohort of CD patients. METHODS: Data were collected prospectively on 44 patients who received adalimumab therapy following infliximab failure. Initial response to adalimumab therapy at 6weeks following induction was defined using a two point decrease in the Harvey-Bradshaw Index, with remission at this point defined using a Harvey Bradshaw index≤4. Sustained clinical benefit at the last point of follow up was determined using a physician's global assessment. Corticosteroid-free sustained clinical benefit was also assessed at this point. RESULTS: Thirty-four (77%) patients had initial response to adalimumab therapy, with 28 (64%) having sustained clinical benefit. Corticosteroid-free sustained clinical benefit was achieved in nine (53%) of 17 patients requiring steroids at commencement of adalimumab. Four (44%) of the 9 patients who were primary non-responders to infliximab responded to adalimumab. The majority of CD patients who failed adalimumab therapy required surgery. CONCLUSIONS: Second-line anti-TNFα therapy with adalimumab is effective at both inducing remission and maintaining response in CD patients who have failed infliximab, regardless of the reason for infliximab failure.

Sinonasal myxoma: a pediatric case.

The authors report a case of a rare facial myxoma arising from the maxillary sinus in a 20-month-old child. The diagnosis was confirmed by a biopsy, and the patient underwent a partial maxillectomy to achieve a total resection of the mass due to the locally aggressive nature of the lesion. Myxomas should be differentiated from malignant sarcomas, in particular embryonal rhabdomyosarcoma, which can arise from the same location and require multimodality therapy consisting of surgery, irradiation, and chemotherapy.